A study of the production and the secretion of the intact pituitary glycoprotein hormone (hTSH), as well as its subunits, offers an ideal model for investigating regulatory mechanisms under a variety of controlled conditions. Nontoxic goiter is the most common endocrine disorder that one encounters in clinical practice. The extra-thyroidal manifestations involve the pituitary, the cardiovascular system, and the breast in females. Enhancing the sensitivity of the radioimmunoassay for hTSH will be helpful in the early diagnosis not only of thyroid disorders but also of their consequences, essential in attempting to obviate the disabling complications of these diseases. Free alpha and beta subunits of hTSH have been found in the serum of hypothyroid patients and their release from the pituitary is under normal feedback control. The concentration of the common alpha subunits is markedly elevated in the serum of patients with certain pituitary tumors and demonstrates abnormal control by positive and negative feedback regulatory mechanisms. It is our plan to pursue this problem in a large group of patients to see if the measurement of the alpha subunit in serum may serve as a marker for diagnosis and the response to therapy in patients with specific pituitary tumors. The animal studies are important in allowing one to expand on the human studies. Studies with the Buffalo rats may serve as an excellent animal model for the patient with decreased thyroid reserve and the concomitant changes involving the pituitary and the breast. The investigations of viable pituitary cells in culure will allow us to study in detail the biosynthesis of TSH, its regulation and control. Such studies could lead to a specific therapy for patients with a pituitary tumor. BIBLIOGRAPHIC REFERENCES: Kieffer, J.D., Mover, H., and Maloof, F: Plasma TSH levels, by radioimmunoassay, during the estrous cycle of the rat. Endocrinology 94: 535, 1975. Kourides, I.A., Weintraub B.D., Ridgway, E.C., and Maloof, F.: Pituitary secretion of free alpha and beta subunit of human thyrotropin in patients with thyroid disorders. J. Clin. Endocrinol. Metab. 40: 872, 1975.